The long term objective of this proposal is the identification of genes responsible for autosomal dominant congenital cataracts, a leading cause of blindness in children. Because of the limitations of studying this ocular disorder in humans, we propose to first devote our attention to mice in order to localize and characterize the candidate genes involved in cataractogenesis. Once identified, the mouse cataract genes can then be utilized to isolate the homologous human genes by hybridizing the mouse genes against a human lens cDNA library. Once the homologous human genes have been characterized, their normal structure i.e., DNA sequence, can be compared to the gene structured in individuals with autosomal dominant cataracts. A candidate gene harboring a mutation in a cataract patient would indicate that this abnormal gene is responsible for the cataract. Gene therapy could then be evaluated in the homologous mouse model which we originally studied for the purpose of preventing cataract formation during the embryonic period. As a starting point for these long term objectives, we propose to focus our studies on 5 independently segregating mutations causing autosomal dominant congenital cataracts in mice. First, we plan to map each abnormal gene to its respective chromosome by microsatellite markers. Second, we will investigate the histopathology of each cataract mutation on the developing lens. Finally, to identify additional independently segregating cataract mutations in mice we will conduct extensive allelism testing of 8 new cataract mutations.